Randomized Phase 2 Study of Atezolizumab and Entinostat in Patients With aTN Breast Cancer With Phase 1b Lead In

Inclusion Criteria

• Has histologically or cytologically confirmed triple negative breast carcinoma that is either metastatic (stage IV of the TNM classification) or locally recurrent and not amenable to local curative treatment.
• Evidence of measurable, locally recurrent or metastatic disease based on imaging studies within 28 days before the first dose of study drug.
• Has received at least 1, but no more than 2, prior lines of systemic therapy for locally recurrent and/or metastatic disease.
• If participant has a history of treated asymptomatic CNS metastases they are eligible, provided they meet all of the following criteria: participant has measurable disease outside CNS; participant does not have metastases to midbrain, pons, medulla or spinal cord; participant is not on corticosteroids as therapy for CNS disease (anticonvulsants at a stable dose are allowed); participant has not had whole-brain radiation within 6 weeks prior to study enrollment; participant has stable CNS disease as demonstrated by at least 4 weeks of stability between the last intervention scan and the study screening scan.
• ECOG performance status of 0 or 1.
• Has acceptable, applicable laboratory parameters.
• Female participants must not be pregnant; willing to use 2 methods of birth control/abstinence if applicable through 120 days after the last dose of study drug.
• Experienced resolution of toxic effect(s) of the most recent prior anti-cancer therapy to Grade 470 msec; uncontrolled hypertension or diabetes mellitus; another known malignancy that is progressing or requires active treatment; active infection requiring systemic therapy; known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Any contraindication to oral agents or significant nausea and vomiting, malabsorption, or significant small bowel resection that, in the opinion of the investigator, would preclude adequate absorption.
• Received a live vaccine within 30 days of the first dose of treatment.
• Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to enrollment or who has not recovered from AEs due to mAb agents administered more than 4 weeks earlier.
• Prior chemotherapy within 3 weeks, targeted small molecule therapy or radiation therapy within 2 weeks prior to enrollment, or who has not recovered (i.e., ≤Grade 1 at enrollment) from AEs due to a previously administered agent.
• Received transfusion of blood products or administration of colony stimulating factors within 4 weeks prior to the first dose of treatment.
• Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study drug.
• Currently receiving treatment with any other agent listed on the prohibited medication list.
• If female, is pregnant, breastfeeding, or expecting to conceive starting with the screening visit through 120 days after the last dose of study drug.
• Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
• Known active hepatitis B or hepatitis C.
• Allergy to benzamide or inactive components of entinostat.
• History of allergies to any active or inactive ingredients of atezolizumab.
• Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.